Introduction
Psychosis is a mental disorder that impacts the way one’s brain decodes or processes information. It involves a combination of pathologic symptoms associated with neurologic, psychiatric, and neurodevelopmental conditions (Calabrese and Khalili, 2020). Antipsychotic medications have long been utilized as primary agents in the treatment and management of the disorder. However, some of these medications can have adverse effects that may exacerbate a patient’s underlying condition. It is the responsibility of healthcare professionals to recommend the most effective medicines to promote optimal outcomes.
The paper is divided into four parts: the first section provides a discussion of the pathophysiology of psychosis. The second segment entails the delineation of the mechanisms of action and drug profiles for olanzapine and aripiprazole. The third portion presents the justification for aripiprazole’s efficacy as an alternative medication for the patient and compliance-related issues. Aripiprazole can be used as an alternative medication to olanzapine. The overall aim of this report is to assess the role of aripiprazole in managing psychosis in a patient and the benefits and harms of the drug as an alternative to olanzapine.
Pathophysiology
Various researchers have examined the mechanisms that underlie the clinical presentation of psychosis. Calabrese and Khalili (2020) identify dopamine as the primary causal agent in the disorder’s pathogenesis. The risk factors associated with psychosis can trigger chronic stimulation, which, in turn, leads to dopamine receptors’ hypersensitization within the nigrostriatal. The aforementioned process may consequently interfere with limbic structures’ functioning responsible for assigning significance to the emotional and hedonic sensory input. These dysfunctions in limbic structures cause the misattribution of internal stimuli originating from external sensory inputs.
Glutamate has also been implicated in the pathogenesis of psychotic conditions. The N-methyl-D-aspartate (NMDA), a glutamate receptor, is a significant element that enhances brain development (Calabrese and Khalili, 2020). Environmental factors such as drug abuse, maternal stress, malnutrition, genetic mutations, and neonatal anesthetic agents can affect the NMDA’s functioning (Calabrese and Khalili, 2020). Alteration in the NMDA receptor’s functioning can subsequently trigger cognitive impairment, which invokes behavioral changes. Alteration of the NMDA receptor during the perinatal period may also interfere with normal brain development, thereby increasing an individual’s susceptibility to developing schizophrenia.
Furthermore, acetylcholine receptors have also been linked with the onset of schizophrenia. For instance, Calabrese and Khalili (2020) associate the alpha7 nicotinic acetylcholine receptor gene (CHRNA7) with the genetic transmission of schizophrenia and the destruction of cognitive functions responsible for psychosocial abilities. Nicotine, which binds to the alpha7 receptor, leads to neurocognitive and neurophysiological defects related to the aforementioned disorder (Clabrese and Khalili, 2020). The factors indicated above are instrumental in the onset and progression of the disorder.
Mechanisms of action and drug profiles
Olanzapine
Olanzapine is an antipsychotic medication utilized in the therapy and management of schizophrenia and bipolar disorders. The drug is indicated for patients with moderate to severe manic episodes. It can also be used to prevent the recurrence of bipolar diseases in patients with a positive drug response history. This medication is well-absorbed when administered orally, and it attains maximum concentrations about six hours after intake. Its elimination occurs extensively via pass metabolism, with around 40% of the dose undergoing metabolism before achieving systemic circulation.
Drug Profile
The following is the drug profile information for Olanzapine (Thomas and Saadabadi, 2020):
- Generic Name: Olanzapine
- Brand Name: Zyprexa, Zolafren, Zyprexa Zydis, Symbyax
- Class: Atypical antipsychotic/ Antipsychotic Agents
- Form: Solid, Yellow crystalline tablets, disintegrating tablets
- Storage temperature: 2 – 8 °C
- Route of Administration: Oral, intramuscular injections
- Dosage: Injectable at 5 mg/mL; oral dosage ranges from 2.5 mg to 20 mg/kg/day depending on the patient’s profile and needs. 20 ng/mL to 40 ng/mL is the drug’s optimal therapeutic window.
- Indications: Patients over 13 years; chronic schizophrenia; bipolar 1 disorder, including mixed and manic episodes; depressive episodes; psychomotor agitation associated with schizophrenia and mania. Olanzapine can be used in combination with Fluoxetine to treat patients aged ten and above who are resistant to depressive treatments. However, the FDA has not approved this indication irrespective of the availability of evidence related to its efficacy (Thomas and Saadabadi, 2020).
- Contraindications: Elderly individuals with dementia and patients hypersensitive to antipsychotic agents. Caution should be taken when dealing with obese and diabetic patients.
- Interactions: Adverse interactions with alcohol. No negative interactivity with food.
- Side Effects: Appetite increase, weight gain, and metabolic effects (insulin sensitivity and impaired glucose tolerance). Although rare, patients can have tardive dyskinesia, akathisia, neuroleptic malignant syndrome, and extrapyramidal symptoms.
Mechanism of Action
Olanzapine exerts its antagonistic action on dopamine D2 and serotonin receptors, particularly serotonin 5HT2A/2C. According to Thomas and Saadabadi (2020), this medication has a high binding affinity for these receptors. Due to its antagonistic nature, olanzapine controls these receptors’ brain activity following the binding process. For example, it prevents the dopamine D2 receptors from acting on postsynaptic receptors by rapidly dissociating the ligand receptors’ kinetics, which, in turn, helps to reduce extrapyramidal symptoms. This antagonistic action can minimize the symptoms associated with psychosis (Thomas and Saadabadi, 2020). For example, the antinausea and antiemetic effects of olanzapine are linked to 5-HT2 and 5-HT3 serotonin receptors’ antagonistic actions (Thomas and Saadabadi, 2020). The information provided above reveals the drug’s efficiency in minimizing psychosis-related manifestations.
Aripiprazole
Background
Aripiprazole is replacing the antipsychotics agents that were previously used as the first-line antipsychotic management. The drug is mainly used in managing schizophrenia and bipolar illnesses, among other conditions. The average eradication half-life of this medication is approximately seventy-five hours following oral administration. Its active metabolite, scientifically referred to as dehydroaripiprazole, is attained at ninety-four hours. The drug reaches steady-state absorption levels within fourteen days after intake. Its peak concentrations in plasma are achieved within three-to-five hours after oral administration. This medicine’s intake of food, especially high-fat meals, does not impact its average plasma levels.
Drug Profile
The following is the drug profile information for Olanzapine (Gettu and Saadabadi, 2020):
- Generic Name: Aripiprazole
- Brand Name: Abilify, Abilitat, Abilify Discmelt
- Class: Antipsychotic Agents
- Form: Solid, flake crystal tablets, solution, and disintegrating tablets
- Route of Administration: Oral, intramuscular injections
- Dosage: Immediate release injections are given at 9.75 mg/1.3 mL while long-acting dosages can be administered at either1064 mg, 441 mg, 662 mg, and 882 mg for 4 to 6 weeks. Oral doses typically vary – from 2 mg to 30 mg/kg/day – depending on the patient’s profile and needs.
- Indications: Schizophrenia, bipolar 1 disorder, including mixed and manic episodes; irritability associated with autistic disorders, depressive disorders; agitation related to schizophrenia and mania, and agitation triggered by dementia, substance use disorders, psychosis, and delirium. The oral and liquid forms are indicated for Tourette syndrome. Although rare, aripiprazole can also cause neuroleptic malignant syndrome, abnormalities in liver function, agranulocytosis, suicidal thoughts in children and adolescents, and death in elderly patients.
- Contraindications: Patients who are hypersensitive to the medication.
- Interactions: Adverse drug interactions with Leuprolide, Goserelin, Desmopressin, and Cyclosporine. This medication has harmful reactions to alcohol and has been linked with no negative interactivity with food. However, patients are required to drink more water to prevent dehydration.
- Side Effects: Nausea, vomiting, lightheadedness, akathisia, off-cycle bleeding, sexual dysfunction, metabolic dysfunction, glucose dysregulation, weight gain, hypercholesterolemia, parkinsonian, and amenorrhea.
Mechanism of Action
The Aripiprazole’s mode of action is unique due to its role as a partial agonist. The drug has a high affinity for 5HT-1a, 5HT2a, D3, and D2 receptors and moderate affinity for H1 receptors, alpha-1 adrenergic, 5HT-2c, 5-HT7, and D4 receptors (Gettu and Saadabadi, 2020). It acts by stabilizing serotonin and dopamine receptors’ action in the brain, resulting in the improvement of cognitive symptoms. Due to its functional selective nature, Aripiprazole does not have many of the extrapyramidal symptoms that have been observed in other antipsychotic medications. Aripiprazole works as a functional antagonist to dopamine receptor activity within the mesolimbic pathway; this particular action is triggered by high dopamine levels (Gettu and Saadabadi, 2020). In areas typified by normal dopamine levels, for instance, the tuberoinfundibular and nigrostriatal pathways, Aripiprazole remains inactive (Gettu and Saadabadi, 2020). Aripiprazole is currently being distinguished as a gold standard in the management of psychotic disorders due to its partial agonist role (Gettu and Saadabadi, 2020). Aripiprazole can also induce the differential expression of genes responsible for the pathogenesis of psychosis in the frontal cortex.
Aripiprazole as an Effective Alternative for the Patient
Aripiprazole can be used as an alternative treatment for the patient due to the following reasons:
The Medication Can Reduce Non-Specific Patho-Psychotic Symptoms
Aripiprazole can reduce psychotic symptoms that result from drug-induced psychosis and symptoms arising from other related conditions such as dementia and bipolar mania. Recent clinical trials associate Aripiprazole with high tolerability and efficacy in managing manic symptoms, both as a monotherapy and when used in combination with mood stabilizers (Sciascio and Riva, 2015). A survey by Gettu and Saadabadi (2020) also reveals the medication’s effectiveness in reducing psychiatric rehospitalization rates, minimizing risk factors associated with cardiovascular conditions, and decreasing tardive dyskinesia symptoms (Gettu and Saadabadi, 2020). As indicated above, this drug has been linked with reduced readmission rates; therefore, the team can use the drug as a strategy for managing this clinical indicator.
The Medication Is Effective in Managing Specific Psychotic Symptoms
Psychosis is mainly characterized by negative symptoms, clinical manifestations, and cognitive decline. The clinical presentations of psychosis include delusions, hallucinations, disorganized thoughts, and behaviors (Calabrese and Al Khalili, 2020). The adverse symptoms include an emotionless or inexpressive state, speech and psychomotor retardation, poor concentration, and loss of interest and contentment in activities that were once gratifying to the patient (Calabrese and Al Khalili, 2020). Evidence shows that Aripiprazole can help better the adverse and clinical symptoms and improve a patient’s cognitive decline. The drug’s partial agonistic nature enhances its efficacy in managing the aforementioned manifestations (Gettu and Saadabadi, 2020; Sciascio and Riva, 2015). The team can achieve optimal patient outcomes by using the drug because of its capacity to treat the condition.
The Medication Has Fewer Adverse Effects Than Olanzapine
Another potential benefit of using aripiprazole is its effectiveness in minimizing extrapyramidal symptoms associated with antipsychotic medications. Aripiprazole has fewer side effects than other antipsychotic agents because of its receptor specificity (Gettu and Saadabadi, 2020). Adverse impacts, for instance, extrapyramidal symptoms and metabolic syndromes are less typical with the medication. Furthermore, extrapyramidal signs, for instance, akathisia, and parkinsonian symptoms such as tardive dyskinesia, resting tremor, and oculogyric crises, can be easily managed with sodium benzoate or benztropine (Gettu and Saadabadi, 2020). Effects such as weight gain, hyperprolactinemia, off-cycle bleeding, and glucose dysregulation are less common when the drug is used. Since the patient has complained of adverse metabolic reactions, aripiprazole might help to alleviate this problem.
The Balance Between the Risks and Benefits
A primary concern linked to Aripiprazole’s prescription for this particular patient is the likelihood of suicidal thoughts. Studies demonstrate the drug’s probability of increasing the risk of suicidal thoughts and behaviors in young adults (Aripiprazole, no date). Given that the patient was initially admitted for self-harm, recommending Aripiprazole may not be in her best interest. On the other hand, some studies have demonstrated that the suicide risks associated with the medication are low for adults aged twenty-four and above. Since the patient is twenty-seven years old, the risk of suicide and its associated perceptions in this patient is low. Regardless of the decision, caution should be taken when prescribing the medication to the patient.
Compliance Issues
Drug noncompliance is a subject of grave concern among psychotic patients. A recent systematic review demonstrated that medication non-adherence among psychotic patients is 60% (Semahegn et al., 2020). Non-adherence can trigger disease exacerbation and minimize medicine’s efficacy (Semahegn et al., 2020). Patients can also become unresponsive to the subsequent treatments due to non-adherence. Other effects of medication non-adherence include increased suicide, rehospitalization, low life quality, symptom relapse, and poor quality of life (Semahegn et al., 2020). Effects such as suicide and rehospitalization have been observed in the patient; these impacts may be associated with noncompliance. Coincidentally, evidence indicates that olanzapine, the medication that was initially prescribed for the patient, effectively reduces suicidal thoughts in psychotic patients (Calabrese and Khalili, 2020). Contrarily, the patient was admitted for self-harm despite using the medication.
To effectively address any problem, it is always crucial to identify the underlying causes. The first cause of nonadherence to the provided medications among psychotic patients is linked to the symptoms associated with the condition (Calabrese and Al Khalili, 2020; Sciascio and Riva, 2015). For example, some studies suggest that psychiatric patients are less likely to comply with prescriptions due to inadequate reasoning (Semahegn et al., 2020). Fear, suspicion, and delirium can also prevent patients from taking their medications.
Targeting these symptoms may help resolve noncompliance to prescriptions among psychotic patients. For example, Sciascio and Riva (2015) demonstrated in their study that the best medication compliance outcomes were obtained when the agitation symptoms associated with schizophrenia and bipolar were remised. The authors also showed that combining aripiprazole and clozapine (an antipsychotic medication) increased a patients’ compliance with the drug (Sciascio and Riva, 2015). This improved compliance level was linked to the reduction of side effects and adverse events of psychotic conditions caused by these medications’ joint function (Sciascio and Riva, 2015). The authors also demonstrated that compliance with aripiprazole was high during the acute phase of the condition and follow-ups (Sciascio and Riva, 2015). In this regard, the team should aim at alleviating the psychotic symptoms in the early stages of the disease to improve compliance. The unit can also create a follow-up routine to encourage medication compliance.
The second cause of nonadherence among psychotic patients is linked to the individual characteristics of the patient. Factors such as lack of family support, patient’s attitude, substance dependency also contributed to medication nonadherence (Semahegn et al., 2020). To overcome these issues, an integrative approach targeting these factors should be considered. According to Semahegn et al. (2020), an integrative approach can result in tremendous positive medication compliance outcomes. The team should strive to create a supportive environment for the patient to reduce the likelihood of noncompliance. They can develop a social support system for the patient and provide her with the resources needed to build her social network. They should liaise with the patient’s family and friends to ensure that the patient has a healthy social support system that can help her cope with the condition and adjust to treatment routines.
Conclusion
Psychosis is a risk factor for schizophrenia and other neurologic degenerative conditions. The condition is characterized by delusions, hallucinations, disorganized thoughts, disorganized behavior, and negative symptom. Aripiprazole can result in positive outcomes in each of these symptomatic domains. Its efficacy in managing the specific psychotic symptoms (positive & negative symptoms) has been established and can be used as an evidence-based drug. The drug works as a partial agonist; it inhibits receptors’ activity in pathways that have high receptor activity but remains inactive in areas with typical receptor activity. I would recommend the medication because the benefits of the medicine surpass the harms. Additionally, the patient is not at risk of the suicidal thoughts and behaviors associated with the medication because of her age. However, caution should still be taken, and the patient should be closely monitored for suicidal behaviors post-discharge. The condition’s symptoms and individual factors may cause the patient not to comply with medication. The interdisciplinary team should closely monitor the patient and create a supportive environment and a social support system to minimize the risk of medication nonadherence.
Reference List
Calabrese, J. and Khalili, Y.A., (2020) Psychosis.Web.
Gettu, N. and Saadabadi, A. (2020) Aripiprazole.Web.
Aripiprazole (no date). Web.
Sciascio, G.D. and Riva, M.A. (2015) “Aripiprazole: from pharmacological profile to clinical use”, Neuropsychiatric Disease and Treatment, 11, pp. 2635–2647. Web.
Semahegn, A., Torpey, K., Manu, A., Assefa, N., Tesfaye, G., and Ankomah, A. (2020) “Psychotropic medication non-adherence and its associated factors among patients with major psychiatric disorders: a systematic review and meta-analysis”, Systematic Reviews, 9, pp. 1-18. Web.
Thomas, K. and Saadabadi, A. (2020) Olanzapine. Web.